Melatonin 1a receptor gene regulatory regions an uses thereof

Abstract

Disclosed are DNAs encoding melatonin 1a receptor gene promoter regions, recombinant polypeptides expressed from such DNAs, and methods of using such expression constructs to screen for promoter activators or inhibitors. Transcriptional activators are useful as therapeutics to reentrain endogenous melatonin rhythms as a means of treating circadian rhythm disorders in humans and control reproductive cycles in seasonally breeding animals. Transcriptional inhibitors are useful as therapeutics to control the initiation or timing of puberty in humans.

I claim: 
     
       1. A method of screening a candidate compound for the ability to alter transcription from a functional melatonin 1a receptor gene promoter, said method comprising: a) providing a cell comprising a recombinant melatonin 1a receptor gene promoter operably linked to a reporter gene;   b) contacting said cell with said candidate compound; and   c) detecting expression of said reporter gene in the presence of said candidate compound, wherein an increase or decrease in said expression in the presence of the candidate compound, compared to expression in the absence of the candidate compound, is an indication that the candidate compound alters transcription from the promoter.   
     
     
       2. The method of claim 1, wherein the melatonin 1a receptor gene promoter is the portion of SEQ ID NO:1 comprising transcriptional and translational regulatory sequences. 
     
     
       3. The method of claim 1, wherein the melatonin 1a receptor gene promoter is capable of hybridizing under stringent hybridization conditions to a nucleic acid molecule having a nucleotide sequence complementary to SEQ ID NO:1. 
     
     
       4. The method of claim 1, wherein the melatonin 1a receptor gene promoter has approximately 95% homology to the transcriptional and translational regulatory region of SEQ ID NO:1. 
     
     
       5. The method of claim 1, wherein the melatonin 1a receptor gene promoter comprises bases -1142 to +26 of FIG. 2 (SEQ ID NO:1). 
     
     
       6. The method of claim 5, wherein the nucleotide sequence further comprises bases +1165 to +1606 of FIG. 2 (SEQ ID NO:1).